Background: Immunostains when used in correlation with clinical site of tumours and morphology permits accurate and specific diagnosis of these undifferentiated tumours. Materials and Methods: A ten-year retrospective research of the histopathological and immunohistochemical features of small round blue cell tumours (SRBCT) in OAUTHC was analyzed. Pathology reports of all SRBCT and their blocks were retrieved and recut slides reviewed to determine each tumour types. Acute myelocytic lymphoma/leukeamias and Glioblastoma multiformis were excluded from SRBCT of childhood. Eighty four (84) cases that fulfilled the inclusion criteria were analyzed using immunohistochemistry. Results: The age range of presentation was 0-15 years (Mean 5.98±3.964 year S.D.). Retinoblastoma and Wilms' tumours were the commonest histological sub-types with a percentage of 20.0% each followed by Burkitt lymphoma (17.6%), rhabdomyosarcoma (9.8%) which was the only soft tissue sarcoma found. The least represented was supra-tentorial CNS-PNET (1.2%). Eighty four blocks of SRBCT were subjected to different panels of immunohistochemistry. Of all these tumours 36 cases had a change in diagnosis: 23 cases had an initial, pre-immunohistochemical umbrella diagnosis ranging from NHL, SRBCT to no pathological diagnosis at all. Seven (7) cases with initial diagnosis ranging from Ewing's sarcoma (1 case), retinoblastoma (1 case) to rhabdomyosarcoma (5 cases) were finally confirmed with immunostains as Burkitt lymphoma (BL) while one case of BL was finally confirmed as rhabdomyosarcoma. The last five of the 36 cases were totally non-neoplastic lesions but had histology diagnosis ranging from NHL, spinal cell sarcoma to periosteal osteosarcoma. The immunostains done on these 5 cases revealed erythroid hyperplasia with dyserythropoiesis, cellular neurofibroma, fibrous dysplasia, reactive follicular hyperplasia and normal retinal tissue. Conclusion: Application of immunohistochemistry does indeed enhance the diagnostic accuracy of these undifferentiated tumors.